Academic Journal
Phosphodiesterase 4 as a therapeutic target in Parkinson's disease recent advances.
| Τίτλος: | Phosphodiesterase 4 as a therapeutic target in Parkinson's disease recent advances. |
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| Συγγραφείς: | Zhong J; Department of Clinical Pharmacy, Meizhou People's Hospital (Huangtang Hospital), Meizhou 514031, China. Electronic address: zhongjiahong@mzrmyy.com., Xu J; Department of Pharmacy, First Hospital of Quanzhou Affiliated to Fujian Medical University, Quanzhou 362000, China., Xue J; Department of Pharmacy, The Second Affiliated Hospital of Shantou University Medical College, Shantou 515000, China., Qiu Z; Department of Clinical Pharmacy, Meizhou People's Hospital (Huangtang Hospital), Meizhou 514031, China., Chen B; Department of Clinical Pharmacy, Meizhou People's Hospital (Huangtang Hospital), Meizhou 514031, China., Yu X; Department of Pharmacy, The Second Affiliated Hospital of Shantou University Medical College, Shantou 515000, China. Electronic address: xihuiyu2016@163.com., Lin Z; Department of Clinical Pharmacy, Meizhou People's Hospital (Huangtang Hospital), Meizhou 514031, China. Electronic address: linzhuomiao@mzrmyy.com. |
| Πηγή: | Experimental neurology [Exp Neurol] 2026 Jun; Vol. 400, pp. 115680. Date of Electronic Publication: 2026 Feb 09. |
| Τύπος έκδοσης: | Journal Article; Review |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Academic Press Country of Publication: United States NLM ID: 0370712 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2430 (Electronic) Linking ISSN: 00144886 NLM ISO Abbreviation: Exp Neurol Subsets: MEDLINE |
| Imprint Name(s): | Publication: Orlando Fl : Academic Press Original Publication: New York. |
| Ιατρικοί όροι (MeSH): | Parkinson Disease*/drug therapy , Parkinson Disease*/metabolism , Parkinson Disease*/enzymology , Cyclic Nucleotide Phosphodiesterases, Type 4*/metabolism , Phosphodiesterase 4 Inhibitors*/therapeutic use , Phosphodiesterase 4 Inhibitors*/pharmacology , Phosphodiesterase 4 Inhibitors*/administration & dosage , Neuroprotective Agents*/therapeutic use , Neuroprotective Agents*/pharmacology, Cyclic AMP/metabolism ; Oxidative Stress/drug effects ; Oxidative Stress/physiology ; Humans ; Animals |
| Περίληψη: | Parkinson's disease (PD), as a common neurodegenerative disorder, is experiencing a continuously increasing incidence worldwide. Patients not only suffer from core motor dysfunction such as tremors, bradykinesia, and muscle rigidity, but also often present with a series of non-motor symptoms including olfactory decline. Phosphodiesterase 4 (PDE4) plays a crucial role in the complex pathological process of PD. As the main hydrolase regulating the intracellular level of cyclic adenosine monophosphate (cAMP), PDE4 is responsible for dynamically regulating this important second messenger molecule with extensive physiological functions. It is worth noting that the dysregulation of the cAMP signaling pathway has been proven to be closely associated with the occurrence and development of neurodegenerative diseases. We will first outline the molecular structural characteristics of PDE4 and its regional and cell-specific distribution in the central nervous system. The focus will be on the multiple and complex roles of PDE4 and the cAMP signal it regulates in the pathogenesis of PD, covering its regulation of networks such as oxidative stress damage, ferroptosis, and endoplasmic reticulum stress (ERS). This paper explores the theoretical basis and latest experimental evidence for the application of PDE4 inhibitors as potential neuroprotective agents or disease-modifying therapies in the treatment of PD. At the same time, it systematically reviews the improvement strategies such as subtype-selective inhibitors, novel drug delivery systems, and structural optimization in response to the key challenges currently faced in the development of PDE4 inhibitors, such as drug selectivity, central permeability, and side effects. Through a systematic analysis of existing research, it deepens the understanding of the regulatory network of PDE4 in PD and provides theoretical basis and forward-looking perspectives for the future development of efficient and safe targeted PDE4 therapeutic drugs and the exploration of new strategies for early prevention and disease process intervention in PD. (Copyright © 2026 Elsevier Inc. All rights reserved.) |
| Competing Interests: | Declaration of competing interest The submission of this manuscript of this work is free from any conflicts of interest, and all authors revised and approved the final manuscript. |
| Contributed Indexing: | Keywords: Neuroprotective agent; Oxidative stress; Parkinson's disease; Phosphodiesterase 4; cAMP |
| Substance Nomenclature: | EC 3.1.4.17 (Cyclic Nucleotide Phosphodiesterases, Type 4) 0 (Phosphodiesterase 4 Inhibitors) 0 (Neuroprotective Agents) E0399OZS9N (Cyclic AMP) |
| Entry Date(s): | Date Created: 20260211 Date Completed: 20260707 Latest Revision: 20260707 |
| Update Code: | 20260707 |
| DOI: | 10.1016/j.expneurol.2026.115680 |
| PMID: | 41672368 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1090-2430 |
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| DOI: | 10.1016/j.expneurol.2026.115680 |